American Urological Association Antibiotic Best Practice Statement and Ureteroscopy: Does Antibiotic Stewardship Help?

Abstract

Purpose:

To determine compliance with the American Urological Association (AUA) antimicrobial prophylaxis best practice statement and whether the use of postoperative antibiotics is associated with lower rates of postoperative urinary tract infection (UTI) in patients with nephroureterolithiasis and a negative preoperative urine culture undergoing ureteroscopy.

Materials and Methods:

A retrospective review of all adult patients undergoing ureteroscopy from 2013 to 2014 for stone disease with a negative preoperative urine was conducted. Patients who did and did not receive postoperative oral antibiotics beyond 24 hours of surgery were identified. The rates of culture-proven postoperative UTI and unplanned postoperative encounters were determined for both groups. Between-group comparisons were made by using independent t-test and Chi-square analyses.

Results:

A total of 1068 patients met inclusion criteria and 31.6% were managed in accordance with the AUA best practice statement by not receiving antibiotics beyond 24 hours of surgery. Overall, 33 patients developed a culture-proven UTI within 30 days after surgery, with no difference in UTI rate between patients who did and did not receive home-going antibiotics (2.9% vs 3.6%, respectively; p = 0.5). Rates of unplanned hospital encounters also did not differ between groups (23.7% vs 27.0%, respectively; p = 0.2). On multivariate regression, culture-proven UTI within 1 year before surgery was the only factor associated with postoperative UTI (odds ratio: 10.8, p < 0.0001).

Conclusions:

Patients who did and did not receive home-going antibiotics after ureteroscopy demonstrated similar rates of postoperative UTI and unplanned hospital encounters. These results suggest that there is no benefit to extended antibiotics after ureteroscopy. The minority of patients managed in accordance with the AUA best practice statement highlights room for quality improvement.

Introduction

Nephroureterolithiasis is an increasingly common condition with an estimated prevalence of 8.8% in the United States in 2010.¹ Technologic advancements in endoscopy have led to increasing use of ureteroscopy in the surgical management of kidney stones.^2,3 Postoperative urinary tract infection (UTI) is a known complication of ureteroscopy and can be prevented, in part, by ensuring urine sterility before surgery.⁴ Further, the American Urological Association (AUA) best practice statement on surgical antimicrobial prophylaxis recommends perioperative antibiotic administration of <24 hours duration at the time of ureteroscopy.⁵ This recommendation is based on evidence that perioperative antibiotics reduce the risk of postoperative pyuria and bacteriuria, though the impact of prophylaxis on reducing the risk of postoperative febrile UTI is less clear.^6
–8

Evidence supporting the use of antibiotics after ureteroscopy is lacking, and it is largely based on extrapolated literature and small retrospective reviews.⁵ Two recent studies found similar rates of postoperative febrile UTI in patients who did and did not receive postoperative antibiotics, in contrast to a third study that showed that postoperative antibiotics were associated with a lower rate of UTI.^9
–11 These studies are limited by their small sample size and a low overall incidence of UTIs, thus limiting comparisons between groups. Further, these studies failed to examine other important considerations of antibiotic administration, including adverse drug reactions, secondary infections, antimicrobial resistance, or cost.¹² With no clear evidence supporting or refuting postoperative antibiotic use, a variety of practice patterns have emerged with as much as one-third of community urologists prescribing postoperative antibiotics beyond what is recommended by the AUA best practice statement.¹³

The hypothesis of this study is that postoperative antibiotic administration does not reduce the rate of UTI after ureteroscopy for stone disease in patients with a negative preoperative urine culture. The primary aim of this investigation was to determine the proportion of such patients managed in accordance with AUA surgical antimicrobial prophylaxis recommendations and to compare rates of postoperative UTI in those who did and did not receive supplemental, home-going antibiotics after ureteroscopy in a large academic system. The second aim of the study was to assess the effect of supplemental home-going antibiotics on the frequencies of unplanned postoperative encounters, such as emergency department visits and telephone calls, as well as on antibiotic-related adverse events.

Materials and Methods

This is a retrospective analysis of patients undergoing ureteroscopy at a large, urban, academic health system from 2013 to 2014. Patients were identified through a query of the electronic medical record by Current Procedural Terminology codes 52352 or 52353 to identify ureteroscopy for kidney stone disease. Patients were excluded from analyses for a positive preoperative urine culture, lack of urine culture within 30 days before surgery, or infection-related stone (i.e., struvite). Patient data were automatically and manually extracted. The institutional review board approved this study.

Clinical and demographic data

All relevant covariates, including patient age at surgery, body mass index (BMI), the presence of antibiotic allergy, diagnosis of diabetes mellitus, preoperative urine culture status, positive urine culture within a year before surgery, intraoperative ureteral stent placement, stone composition, duration of ureteroscopy, and details of home-going oral antibiotic prescriptions, were recorded. Patients in the cohort were stratified based on discharge with or without home-going antibiotics. Clinical outcomes within 30 days after surgery were postoperative urine culture and unplanned encounters, including postoperative telephone calls and/or emergency room visits. Clinical outcomes were confirmed with chart review to be surgically relevant, and unrelated encounters (i.e., unrelated chronic conditions) or those as part of routine follow-up were excluded.

A positive urine culture was defined as >50,000 colony-forming units per milliliter of a single pathogenic organism. Pyuria was defined as 10 or more white blood cells per high-powered field or moderate to large leukocyte esterase on preoperative urinalysis. Primary stone composition was defined as ≥50% of one stone type on analysis. Unplanned encounters: telephone calls and emergency department visits were categorized as: (1) suspected postoperative infection (fever, malaise, or other constitutional symptoms); (2) antibiotic-related adverse events (gastrointestinal upset, rash, yeast infection); (3) postoperative pain; or (4) other urologic complaints (catheter problems, hematuria).

Statistical analyses

Simple descriptive statistics were performed, and data were presented as means and standard deviations. Univariable analyses were conducted by using Student's t-test for continuous variables, based on normally distributed data, and categorical variables were compared by using Chi-square analysis, with Fisher's exact test as indicated for small cell sizes. A multivariable regression analysis was performed for postoperative culture-proven UTI with relevant univariable factors, including age, gender, BMI, diabetic status, operative time, home-going antibiotics, intraoperative stent placement, and positive urine culture 1 year before surgery. All statistical tests were two-sided, with p < 0.05 indicating statistical significance. All statistical analyses were performed by using JMP Pro 12 (SAS Institute, Inc., Cary, NC).

Results

A total of 1722 patients were identified across 4 hospitals within the health system. The sample comprised surgical cases from 9 urologists who regularly perform endourologic procedures. From the original sample of 1722 patients, 458 patients were excluded for lacking a preoperative culture within the 30 days before surgery, and 196 were excluded for positive preoperative urine cultures. Of the remaining, 1068 patients were included in analyses and adherence to the AUA antibiotic best practice statement was 31.6% (n = 337) in this sample. The major stone composition of the group was Calcium Oxalate (38%) followed by calcium phosphate (17%).

Groups of patients (Table 1) who did and did not receive supplemental, oral, home-going antibiotics did not differ with regard to gender, age, presence of an antibiotic allergy, prevalence of diabetes mellitus, and operative time. However, patients who received supplemental antibiotics had a significantly greater BMI (30.52 ± 7.33 vs 29.59 ± 5.57 kg/m², p = 0.0394) and were significantly less likely to have undergone intraoperative stent placement (32.4% vs 40.1%, p = 0.0149). The types of supplemental antibiotics given included amoxicillin (n = 10), amoxicillin-clavulanate (n = 13), trimethoprim-sulfamethoxazole (n = 137), ciprofloxacin (n = 437), cephalexin (n = 88), and nitrofurantoin (n = 33). Perioperative antibiotic prophylaxis consisted of amoxicillin (n = 4), ampicillin (n = 12), cefazolin (n = 349), ciprofloxacin (n = 344), gentamicin (n = 131), vancomycin (n = 58), piperacillin-tazobactam (n = 29), or other antimicrobials (n = 123).

Table 1.

Study Sample

	Total sample	Supplemental home-going antibiotics	No supplemental antibiotics	p
Number, n (%)	1068 (100)	731 (68.4)	337 (31.6)	—
No. of women, n (%)	514 (48.1)	358 (48.97)	156 (46.3)	0.415
Age ± SD (years)	54.5 ± 15.6	54.0 ± 15.9	54.9 ± 15.4	0.346
BMI ± SD (kg/m²)	30.22 ± 7.11	30.52 ± 7.33	29.59 ± 6.57	0.039
Antibiotic allergy, n (%)	303 (28.4)	197 (26.95)	106 (31.45)	0.129
Preoperative pyuria	233 (21.8)	164 (22.4)	69 (20.5)	0.52
Diabetes mellitus, n (%)	259 (24.3)	183 (25.03)	76 (22.55)	0.379
Operative time ± SD (minutes)	54.63 ± 15.57	54.94 ± 15.42	53.96 ± 15.89	0.346
Intraoperative stent placement, n (%)	372 (34.8)	237 (32.4)	135 (40.1)	0.0149
UTI within a year earlier	158 (14.8)	106 (14.5)	52 (15.4)	0.691

Bold text indicates p < 0.05.

BMI = body mass index; SD = standard deviation; UTI = urinary tract infection.

A total of 33 patients (3.09%) developed a postoperative culture-proven UTI (Table 2), and rates of UTI did not differ with or without home-going antibiotic prescription (2.87% vs 3.56%, p = 0.546). On univariable and multivariable analyses, postoperative UTI was not associated with differences in age, gender, BMI, antibiotic allergy, preoperative pyuria, intraoperative stent placemen, diabetic status, operative time, or the prescription of supplemental home-going antibiotics. On univariable analysis, a culture-proven UTI (positive urine culture) within the year before surgery was significantly associated with postoperative UTI (12.7% vs 1.43%, p < 0.0001). On multivariable regression, culture-proven UTI (positive urine culture) within 1 year of surgery was the only factor significantly associated with postoperative UTI (odds ratio = 10.8, p < 0.0001).

Table 2.

Postoperative Course by Home-Going Antibiotic Status

	Supplemental home-going antibiotics (n = 731), n (%)	No supplemental antibiotics (n = 337), n (%)	p
Culture-proven postoperative UTI	21 (2.87)	12 (3.56)	0.546
Surgically-related emergency room visit or telephone call	173 (23.7)	91 (27.0)	0.240
Surgically-related emergency room visit	26 (3.56)	17 (5.04)	0.250
Surgically-related telephone call	162 (22.2)	85 (25.2)	0.270
Emergency room visit or telephone call for possible infection	27 (3.69)	13 (3.86)	0.896
Emergency room visit for possible infection	7 (0.96)	1 (0.30)	0.447
Telephone call for possible infection	22 (3.01)	12 (3.56)	0.633
Possible antibiotic adverse event	20 (2.74)	7 (2.08)	0.524

Post hoc analysis (Table 3) of patients who had a UTI within 1 year before surgery revealed that those given home-going antibiotics after ureteroscopy experienced no difference in postoperative UTI rate than those who did not receive supplemental treatment (11.32% vs 15.38% p = 0.458, respectively). Similar rates were observed for those with no UTI the year before surgery if home-going antibiotics were or were not prescribed (1.44% vs 1.40%, p = 1.000, respectively). When stratified by home-going antibiotics, increased rates of postoperative UTI remained significantly higher in those having a UTI in the year preceding ureteroscopy with (11.32% vs 1.44%, p < 0.0001) or without (15.38% vs 1.40%, p < 0.0001) supplemental antibiotics.

Table 3.

Postoperative Course by UTI history

	No postoperative UTI	Postoperative UTI	p
Those who received home-going antibiotics, n (%)
UTI within 1 year of ureteroscopy	616 (98.6)	9 (1.44)	<0.0001
Prior UTI	94 (88.7)	12 (11.3)
Those who received no home-going antibiotics, n (%)
No UTI within 1 year of ureteroscopy	281 (98.6)	4 (1.4)	<0.0001
Prior UTI	44 (84.6)	8 (15.4)

Rates of unplanned postoperative encounters did not differ based on whether patients were prescribed supplemental home-going antibiotics or not (Table 2). Rates of stent placement significantly differed between patients who did and did not receive home-going antibiotics (32.4% vs 40.1%, p = 0.0149). When stratified by stent placement, the rates of unplanned postoperative encounters were similar between patients who did and did not receive home-going antibiotics (Tables 4 and 5). Independent of antibiotics, stented patients had a higher rate of unplanned encounters when compared with patients without stents (29.8% vs 22.0%, p = 0.005).

Table 4.

Postoperative Course With Stent Placement With or Without Antibiotics

	Stent placed + antibiotic, n (%)	Stent placed no antibiotic, n (%)	p
Sample size (% stented group; n = 372)	237 (63.7)	135 (36.3)	—
Culture-proven postoperative UTI (% stented group; n = 372)	8 (3.38)	6 (4.44)	0.602
Surgically-related emergency room visit or telephone call (% stented group; n = 372)	71 (29.96)	40 (29.63)	0.947
Surgically-related emergency room visit (% stented group; n = 372)	12 (5.06)	5 (3.70)	0.616
Surgically-related telephone call (% stented group; n = 372)	68 (28.69)	39 (28.89)	0.968
Emergency room visit or telephone call for possible infection (% stented group; n = 372)	7 (2.95)	4 (2.96)	1.000
Emergency room visit for possible infection (% stented group; n = 372)	3 (1.27)	0 (0.00)	0.556
Telephone call for possible infection (% stented group; n = 372)	6 (2.53)	4 (2.96)	1.000
Possible antibiotic adverse event (% stented group; n = 372)	10 (4.22)	2 (1.48)	0.224

Table 5.

Postoperative Course Without Stent Placement With or Without Antibiotics

	No stent + antibiotics, n (%)	No stent no antibiotic, n (%)	p
Sample size (% no stent group)	494 (71.0)	202 (29.0)
Culture-proven postoperative UTI (% no stent group)	13 (2.63)	6 (2.97)	0.803
Surgically-related emergency room visit or telephone call (% no stent group)	102 (20.65)	51 (25.25)	0.184
Surgically-related emergency room visit (% no stent group)	14 (2.83)	12 (5.94)	0.050
Surgically-related telephone call (% no stent group)	94 (19.03)	46 (22.77)	0.263
Emergency room visit or telephone call for possible infection (% no stent group)	20 (4.05)	9 (4.46)	0.807
Emergency room visit for possible infection (% no stent group)	4 (0.81)	1 (0.50)	0.656
Telephone call for possible infection (% no stent group)	16 (3.24)	8 (3.96)	0.636
Possible antibiotic adverse event (% no stent group)	10 (2.02)	5 (2.48)	0.775

Antibiotic-related adverse events were only noted in telephone calls and none were observed at emergency department visits. A total of 27 patients (2.5% of the cohort) reported an antibiotic-related adverse event, and rates did not differ between patients who did and did not receive home-going antibiotics (2.7% vs 2.1%, p = 0.524, respectively). No serious adverse events occurred whether or not home-going antibiotics were prescribed, with 26 patients reporting gastrointestinal symptoms (2.3% vs 2.7%, p = 0.831, respectively) and 7 reporting rash (0.7 vs 0.6%, p = 1.000, respectively). There were no reported cases of Clostridium difficile colitis or anaphylaxis in the cohort.

Discussion

In the recently updated AUA/Endourological Society 2016 guidelines for the surgical management of stones, the committee recommends a single dose of appropriate oral or intravenous antibiotics within 60 minutes of surgery for patients with negative preoperative urine culture undergoing uncomplicated ureteroscopy.¹⁴ This best practice recommendation for perioperative antibiotic prophylaxis does not favor prolonged antibiotic use, and it has remained unchanged since 2008.⁵ In fact, several studies have demonstrated that antibiotic prophylaxis for 24 or more hours does not decrease the rate of UTI.^8,9,11 However, there is a great deal of variation in practice pattern, as was evidenced in this study. Specifically, 69.4% of practitioners analyzed prescribed supplemental antibiotics, which did not appear to provide any meaningful reduction in the rate of UTI or unplanned hospital encounters. Although this study was not designed to ascertain the rationale underlying extended antibiotic use, discussions with the surgeons suggest that concern for a catastrophic event (i.e., urosepsis) and desire to decrease unplanned encounters primarily drive their prescribing patterns.

The overall rate of UTI was 3.1% in the study sample, and there was no significant difference between the rates of postoperative UTI in patients treated with less than or greater than 24 hours of antibiotics. Wolf and colleagues identified high-risk patients who may benefit from extended antibiotic prophylaxis after ureteroscopy, which included those with placement of a foreign body into the urinary tract, such as urinary catheters, as well as pre-existing UTI, and manipulation of an indwelling urinary tube.⁵ Based on these risk factors, this study excluded all patients who had a positive preoperative urine culture. Placement of an intraoperative stent,¹⁵ duration of surgery,¹⁰ and BMI were analyzed with regard to their effects on the primary and secondary outcomes in this study. Only the presence of a UTI within 1 year before surgery was associated with postoperative UTI. To better understand the influence of previous UTI, a stratified analysis was performed based on home-going antibiotic status. A clinically significant but not statistically significant reduction (15.38%–11.32%) in postoperative UTI was achieved in patients with UTI the year preceding ureteroscopy. However, those without an infection the year leading into surgery did not see a reduction (1.40%–1.44%) in postoperative infection rates with or without antibiotics. This suggests that perhaps the best group to target with home-going antibiotics may be patients with a history of UTI over the past year.

Moses and colleagues demonstrated an increased rate of unplanned hospital returns among 550 patients discharged without home-going antibiotic prescriptions in compliance with the AUA best practice statement.¹⁰ This observation was based on 19 unplanned emergency department visits in their study sample. In this study, there were 43 (4.0%) emergency department visits and 247 (23.1%) telephone encounters among the 1068 patients studied. There was no significantly increased rate of unplanned encounters on univariate analysis among patients treated in accordance with the AUA best practice/guideline recommendations. However, it is important to note that the rate of compliance with the AUA best practice/guidelines recommendation in the Dartmouth study was 48.7% and is higher than the 31.6% rate observed in this study. Nonetheless, there was no benefit of prolonged antibiotics observed in this study, despite 69.4% of patients receiving them.

Although antibiotics are necessary to treat and prevent infections, antibiotic overuse is associated with negative sequelae, including medication side effects, opportunistic infections, and antibiotic resistant organisms.^16
–18 Considering this, the Centers for Disease Control released a 2014 call for antibiotic stewardship, which charged physicians to improve prescribing practices.¹⁹ Despite lacking level one evidence for the role of antibiotics in several areas of urology, it is critical for urologists to scrutinize antibiotic use. For example, one study by Swartz et al. retrospectively reviewed postoperative antibiotic use at the time of synthetic midurethral sling surgery and found an increased rate of antibiotic-related adverse events in the group that received postoperative oral antibiotics compared with those who received only preoperative antibiotic prophylaxis. The findings of this study subsequently led to a change in practice within the instutition.²⁰ Similarly, as a result of this study, there is an ongoing quality initiative to address the use of antibiotics after ureteroscopy.

Limitations of this study include its retrospective design, which subjects its findings to selection bias. Particularly, it is unclear whether patients who received antibiotics had confounding risk factors for infection that were not captured by the variables analyzed. As such, it is possible that these unidentified high-risk patients selectively received prolonged antibiotics after their procedure, which normalized their rates of infection after surgery. Large randomized controlled trials are needed to eliminate this bias, which is inherent to all of the retrospective studies reported thus far. Second, given the small reported rate of postureteroscopy UTI, the power needed to detect a small difference in the rates of postoperative UTI with or without supplemental antibiotics requires the randomization of several thousand men to each treatment arm. This remains a limitation in the other prior studies as well; however, it should be noted that this study represents the largest sample analyzed to date. Third, data are lacking regarding the duration of postoperative antibiotic treatment, medication compliance, and standard protocols among the nine urologists. These clinical parameters could be helpful in identifying risk factors for adverse outcomes, such as postoperative infection, that many clinicians strive to minimize with prolonged antibiotic therapy. Overall, this study identified no benefit of prolonged antibiotics after ureteroscopy in a large sample of patients from a multisite academic system consisting of experienced endourologists.

Conclusions

Prolonged antibiotic treatment did not reduce postoperative UTIs among patients with negative preoperative urine culture undergoing ureteroscopy for stone disease. Although no difference was noted in the rates of antibiotic-related adverse effects within 30 days of surgery, urologists should strive to practice good antibiotic stewardship in compliance with the new AUA guidelines to reduce potential morbidity and cost to patients.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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